N-acetylcysteine ​​(NAC) is an acetylated form of the amino acid cysteine​​. it exerts its mucolytic action through its free sulfhydryl group, which opens the disulfide bonds and lowers mucus viscosity. NAC has been demonstrated to cause a decrease in sputum consistency, to facilitate easier expectoration, and to increase sputum volume, making it a drug of choice in many respiratory diseases characterized by thick secretions.

N-acetylcysteine is a precursor of glutathione as well. Glutathione is a potent antioxidant that cannot cross the cell membranes, but N-acetylcysteine easily crosses it and is converted to cysteine, an amino acid essential for the synthesis of glutathione.

At therapeutic doses, 90% of acetaminophen (Paracetamol) is metabolized in the liver to sulfate and glucuronide conjugates that are then excreted in the urine. A small portion of acetaminophen is oxidized by CYP2E1 to form N-acetyl-p-benzo-quinone imine (NAPQI). NAPQI binds covalently with hepatocyte macromolecules, producing hepatic cell lysis. With normal doses, NAPQI is rapidly conjugated with hepatic glutathione, forming a nontoxic compound which is excreted in the urine.

Liver damage due to excess NAPQI can occur in many circumstances (e.g. excessive intake of acetaminophen, excessive CYP2E1 activity due to induction by other drugs or chronic alcohol use, Competition for conjugation enzymes, depletion of glutathione stores due to malnutrition or chronic alcohol ingestion), in these circumstances, N-acetylcysteine can be administered orally or IV as an antidote to prevent or lessen hepatic injury.

Serious anaphylactoid reactions, including death in a patient with asthma, have been reported in patients administered acetylcysteine intravenously. Acute flushing and erythema of the skin may occur in patients receiving acetylcysteine intravenously. These reactions usually occur 30 to 60 minutes after initiating the infusion and often resolve spontaneously despite continued infusion of acetylcysteine. Anaphylactoid reactions (defined as the occurrence of an acute hypersensitivity reaction during acetylcysteine administration including rash, hypotension, wheezing, and/or shortness of breath) have been observed in patients receiving I.V. acetylcysteine for acetaminophen overdose and occurred soon after initiation of the infusion. If a reaction to acetylcysteine involves more than simply flushing and erythema of the skin, it should be treated as an anaphylactoid reaction. This usually entails administering antihistaminic drugs (chlorphenamine 10-20 mg IV over 1 min) and in severe cases may require administration of epinephrine and salbutamol nebs (if significant broncospasm). In addition, the acetylcysteine infusion may be interrupted until treatment of the anaphylactoid symptoms has been initiated and then carefully restarted. If the anaphylactoid reaction returns upon reinitiation of treatment or increases in severity, intravenous acetylcysteine should be discontinued and alternative patient management should be considered.

Use with caution in patients with asthma, or where there is a history of bronchospasm.